New and emerging viruses and arboviruses represent increasing threats to human health, yet their mechanisms of emergence remain poorly understood, and effective interventions are not available for most. Research on their ecology, evolution, epidemiology, emergence mechanisms, diagnostics, and development of vaccines and therapeutics remain critical public health needs. The World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) comprises a comprehensive, diverse collection of over 6,700 virus strains in 21 families, as well as antisera, antigens and other reagents to enable research worldwide. Approximately 400 new virus strains are added each year, and 1000 viruses and reagents are shipped annually. The WRCEVA also maintains broad expertise in both novel and traditional approaches to virus identification and characterization, and assists with outbreak diagnosis. This proposal seeks to continue these WRCEVA activities in support of NIH-funded and other research on emerging viruses worldwide through 5 Specific Aims: 1. Maintain a comprehensive set of emerging viruses, arboviruses and associated reagents to support research and surveillance. The virus collection as well as antigens, antibodies and other reagents will be continually enhanced to capitalize on new technology, and cDNA clones of selected strains will be added. NextGen sequencing-based quality control practices will be implemented to ensure strain accuracy/purity. 2. Discover, isolate and characterize newly acquired viruses by using electron microscopy, next generation sequencing, and serologic methods to determine relationships and taxonomic assignments, and to assess in vitro and in vivo host range. Clinical and field samples as well as viral isolates will be received for identification and characterization, and added to the repository. Critical phenotypes of newly discovered viruses and strains will be assessed by using in vitro and in vivo infections. 3. Perform sequencing and phylogenetic analyses of selected virus groups to determine evolutionary histories and emergence mechanisms, patterns of spread and infection, and to rapidly determine the sources of new outbreaks. Key virus strains will undergo genomic sequencing to generate databases that can be exploited for the rapid determination of new outbreak sources, including potential bioterrorism. 4. Characterize recently discovered mosquito-specific viruses (MSVs) and determine their evolutionary history, impact on the transmission of arboviruses, and genetic determinants of host range. Selected arbovirus taxa that include mosquito-specific viruses will be studied to understand the genetic basis of their host range restriction and assess their potential as tools to interfere with arbovirus transmission 5. Train scientists in the identification and characterization of emerging viruses and arboviruses. To further enhance research efforts in the U.S. and worldwide as well as to leverage collaborations that feed our collections, basic training in virus identification and characterizaton will be provided to qualified scientists.